1. Field of the Invention
The present invention relates to compositions and methods for inhibiting reverse transcription, and, more particularly, to such compositions and methods for creating a nucleoside analog that disrupts the hybridization step during reverse transcription.
2. Description of Related Art
Retroviruses contain RNA rather than DNA as the genetic material. Those such as that believed responsible for acquired immune deficiency syndrome (AIDS), the human immunodeficiency virus (HIV), function by utilizing the enzyme RNA-dependent DNA polymerase, or reverse transcriptase, to create a DNA strand from the viral RNA for directing viral infection and synthesis within a host system.
It is well known in the art to introduce nucleoside analogs into the host that block reverse transcription from manufacturing DNA by presenting faulty substrates to the enzyme that compete with the naturally occurring nucleosides for incorporation into a DNA strand. For example, azidothymidine (AZT; Retrovir, Burroughs Wellcome) is widely used in cases of HIV infection.
A suggestion has also been made to use L-nucleosides as analogs. Weis et al. (U.S. Pat. Nos. 5,559,101 and 5,672,594) disclose the use of L-ribofuranosyl nucleosides as an antiviral composition.
Lin et al. (U.S. Pat. Nos. 5,561,120; 5,627,160; and 5,631,239) teach the use of dideoxynucleoside analogs containing a dideoxy ribofuranosyl moiety having an L-configuration as an anti-retroviral agent, particularly for HBV. The '160 patent additionally discloses the use of 1-(2,3)-dideoxy-.beta.-L-ribofuranosyl)-5-fluorocytosine as a potent anti-HIV agent.
Chu et al. (U.S. Pat. Nos. 5,565,438; 5,567,688; and 5,587,362) describe L-nucleoside analogs for treatment of HBV or EBV. The sugar moiety illustrated comprises a 5-membered 2'-fluorinated ring.
It is known, however, that at least some of the previously tested antiviral agents have negative side effects such as cytotoxicity and also limited effectiveness owing to inactivation or digestion prior to reaching the target.